Grant: Doctoral: Vanier Canada Graduate Scholarships

Inflammatory bowel disease (IBD) is thought to result from damage to the intestinal barrier, which allows bacteria or food components to leak across the intestine and interact with the immune system. Interestingly, dietary fat may play a role in the cause and/or prevention of IBD; high n-6 fatty acids (FAs) have been linked to a higher incidence of IBD in Japan, while n-3 FAs may play a role in promoting the intestinal barrier. It is unknown if n-3 FAs act directly, or indirectly by altering bacteria or activating innate receptors. Recent studies show that activation of innate receptors, called toll-like receptors (TLR) by bacteria promote intestinal barrier function. Interestingly, mice deficient (-/-) in TLR2 have been shown to develop more severe IBD than normal mice. It is hypothesized that n-3 FAs and TLRs promote barrier integrity through independent means. Objective 1: To assess whether n-3 FA's protect intestinal barrier via changes in bacteria and/or TLR signaling. To address if bacteria are required for the actions of n-3 FAs during IBD, we will treat mice with antibiotics to reduce the intestinal bacteria. Mice will undergo IBD induction, and intestinal tissues will be assessed for damage. To further address the roles of bacteria and TLRs, the diets of normal and TLR2-/- mice will be supplemented with n-3 FAs, following which IBD will be induced. Any impact of n-3 FAs on commensal populations will be assessed. Objective 2: To define the mechanisms underlying the role of n-3 FAs in maintaining barrier integrity. Using a similar approach, the protective actions of n-3 FAs will be studied both prior to and during IBD. Intestinal cell growth, function and death, as well as inflammation will be measured. Significance: Findings will help determine if n-3 FAs may be useful in preventing and/or treating intestinal conditions such as IBD.